Methacholine Provocation Research Articles

Comparison of the bronchodilating effects of inhaled β2-agonists after methacholine challenge in a human lung reperfusion model

The aim of the present investigation was to compare the onset of action and intrinsic activity of the long-acting β2-agonist GW597901 with the fast- and short-acting salbutamol as model compounds using an isolated human lung reperfusion model. Twelve resected human lung lobes were challenged with methacholine (MCh) and subsequently nebulised with either GW597901 or salbutamol. Prostaglandin E2 (PGE2) concentrations in the perfusion fluid were compared with the dose of MCh that was required to induce a bronchoconstriction. After successful MCh provocation, nebulisation of GW597901 and salbutamol fully reversed any observed bronchoconstriction. The bronchodilating effect was more pronounced for GW597901. Salbutamol revealed an immediate onset of action while the effect of GW597901 was observed with an approximate delay of 6min. Higher doses of MCh were required for a successful bronchial challenge in the presence of elevated PGE2 levels (r=0.8171, p⩽0.05). For the first time, an isolated perfused human lung model has been established for comparing the onset of action and potency of a short- and long-acting β2-agonist. We therefore conclude that it is an alternative for determination of drug effect characteristics and suitable for supplementing or predicting clinical data.

Aeroallergen‐induced hypoxic bradycardia in spontaneously breathing house dust mite‐sensitive nonhuman primates

RATIONALEA small number of house dust mite (HDM)‐sensitive nonhuman primates (NHP) exhibit life‐threatening bradycardia after aero‐HDM challenge. Retrospective analysis was performed to elucidate conditions associated with the adverse cardiac response.METHODSData recorded for 71 NHP over 4 years was screened for a >25% decrease in HR and minimum HR <100 bpm following HDM challenge. Prior to data acquisition, NHP were anesthetized, intubated, and instrumented to record SpO2 & HR, lung resistance (RL), and dynamic compliance (Cdyn).RESULTSHypoxic bradycardia was observed in 10 of 71 NHP. It was associated with airway sensitivity to HDM and was preceded by rapid‐shallow breathing and often apnea. HR decreased 50% to 76±6 bpm and was associated with an SpO2 of 71±4%, increase in RL of 139±37%, and decrease in Cdyn of 59±5%. Bradycardia was also observed during methacholine provocation performed 24 hours after HDM challenge. Bradycardia was reversed by mechanical ventilation or atropine.CONCLUSIONSHypoxic bradycardia during respiratory stasis has been described in humans and canines. Our data indicate that HDM‐allergy can lower O2 and tidal volume thresholds for the reflex in susceptible subjects.

Comparison of methacholine and mannitol bronchial provocation tests in workers with occupational asthma

Comparison of methacholine and mannitol bronchial provocation tests in workers with occupational asthma

The interest of FEF25–75 in evaluating bronchial hyperresponsiveness with the methacholine test

BackgroundBronchial hyperresponsiveness is the pathogenic basis of asthma, and measurement of its intensity is investigated using the methacholine provocation test, which not only and particularly evaluates the reduction in FEV1 (PD20) but also takes forced mid-expiratory flow or FEF25–75 (PD40) into account. The present study aims to evaluate the usefulness of both parameters. Material and methodsProvocation testing was carried out in 151 patients between 7 and 22 years of age diagnosed with asthma, tracheobronchitis and/or rhinitis, using a short method that allows quantification of the methacholine administered. The subjects were divided into three groups according to the amount of methacholine needed to obtain the mentioned parameters (group 1: ≤1000μg; group 2: 1001–2000μg; group 3: ≥2001μg). ResultsGreater variability was recorded for FEF25–75 than for FEV1. Paired comparison among the three groups for FEV1 proved significant, in the same way as for FEF25–75 between groups 2 and 3, and 1 and 3, but not between groups 1 and 2. Calculation was made of the amount of methacholine required to obtain PD20 and PD40 from the same dose. Only the significant differences corresponded to the comparison of group 1 versus the rest, with no differences between the means of the total mean values. ConclusionsThe utility of PD20 is more evident, considering the variability of PD40; the latter may be useful in patients with rhinitis or tracheobronchitis when PD20 proves scantly demonstrative.

Acute respiratory effects in firefighters

Associations between acute respiratory inflammatory responses, changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and exposure to fire smoke were studied. The study comprised 51 firefighters. Blood samples were taken within 24 hr following exposure to fire smoke, and after a week and 3 months. Sputum was induced within 5 days post-exposure and subjects underwent spirometry and methacholine provocation one week post-exposure. Exposure was registered by a questionnaire. No changes were observed following smoke exposure in bronchial hyperresponsiveness and serum pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters (44%) elevated sputum neutrophil levels (≥60%) were found. Serum IL-8 concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated neutrophil levels in sputum were associated with elevated serum IL-8 (β = 0.010, P = 0.004) and TNFα (β = 0.005, P = 0.034) levels within 24 hr post-exposure and IL-8 elevation lasted up to 3 months. Acute exposure to fire smoke induces acute neutrophilic airway and long-lasting systemic inflammation in healthy firefighters in the absence of bronchial hyperresponsiveness.

Sevoflurane and desflurane protect cholinergic-induced bronchoconstriction of hyperreactive airways in rabbits

The potential of desflurane to alter respiratory mechanics in the presence of bronchial hyperresponsiveness (BHR) is still a subject of debate. Accordingly, we evaluated the bronchoprotective potential of desflurane compared with sevoflurane following cholinergic lung constriction in rabbits with normal and hyperreactive airways. The input impedance of the respiratory system (Zrs) was measured during midazolam-based anesthesia before and during intravenous infusions of increasing doses of methacholine (MCh). The rabbits in the control group (Group C) were then randomized to receive either sevoflurane 1 MAC followed by desflurane 1 MAC or vice versa, whereas ovalbumin-sensitized rabbits received sevoflurane followed by desflurane (Group S-SD) or vice versa (Group S-DS). Baseline Zrs measurements and the MCh provocations were repeated under the maintenance of each volatile agent. Airway resistance (Raw), tissue damping (G), and elastance data were obtained from Zrs by model fitting. Similar bronchoprotective effects of sevoflurane and desflurane against MCh-induced bronchoconstriction were observed independently of the severity of the bronchospasm and the presence of BHR. With sevoflurane, the decreases in Raw ranged from 22 (8.8)% to 44 (12)%, and with desflurane, they ranged from 22 (8.7)% to 50 (12)%. The increases in G reflecting the enhanced ventilation heterogeneities in the lung periphery were not affected by the volatile agents. If the contractile stimulus is cholinergic in origin, sevoflurane and desflurane exert similar bronchoprotective potentials to act against lung constriction independent of the presence of BHR. These volatile anesthetics otherwise lack a potential to improve the enhanced ventilation heterogeneities that develop particularly in the presence of BHR.

Respiratory health in firefighters

ObjectivesThe aim of the present study was to determine associations between respiratory health and exposure to smoke of fires.MethodsThe studies comprised 3 subsequent stages. First, all active firefighters of the...

The effect of caffeinated coffee on airway response to methacholine and exhaled nitric oxide

The bronchoprotective effect of caffeine on histamine challenge testing (HCT) has been studied with equivocal results. Current guidelines for bronchoprovocation testing recommend exclusion of caffeine the day of testing. The effects of caffeine on methacholine challenge testing (MCT), now more commonly performed than histamine challenge, are unknown. Sixteen well-controlled asthmatics with a forced expiratory volume in 1 s (FEV(1)) > 65% predicted and methacholine provocation concentration causing a 20% fall in FEV(1) (PC(20)) ≤ 16 mg/ml participated in a randomized single-blind crossover study. The two treatments included 16 ounces of caffeinated and decaffeinated coffee given on two separate days. The fraction of exhaled nitric oxide (eNO) and FEV(1) were measured before and 1 h after each treatment. One hour post treatment blood was drawn for serum caffeine level and the MCT was done. Fourteen subjects completed the study; there were no adverse events. No significant bronchodilation was seen between the mean FEV(1) values before and after the caffeinated treatment (3.31 ± 0.75 L and 3.36 ± 0.74 L, respectively). No significant bronchoprotection was seen between the caffeinated and decaffeinated treatment's geometric mean PC(20) values (1.35 mg/ml and 1.36 mg/ml, respectively). Mean eNO values before and after caffeinated treatment were not significantly different (31.2 ± 19.6 ppb and 31.5 ± 20.4 ppb). The amount of caffeine in a normal dietary serving of a 16 oz cup of coffee is not enough to cause significant bronchoprotection, bronchodilation, or decrease eNO values. Registered at http://clinicaltrials.gov: NCT01057875.

Sensitivity to Environmental Irritants and Capsaicin Cough Reaction in Patients with a Positive Methacholine Provocation Test before and after Treatment with Inhaled Corticosteroids

Background. Increasing evidence points to a potential role for members of the transient receptor potential family of cation channels on several features of asthmatic disease. The cough sensitivity to inhaled capsaicin is known to reflect the reactivity of these airway sensory nerves. Objective. The aim was to study, among patients having a positive methacholine provocation and diagnosed with asthma, capsaicin cough sensitivity, sensitivity to methacholine, and levels of exhaled nitric oxide before and after treatment with inhaled steroids, and further, to measure the self-reported impact from environmental irritants. Methods. Eighteen steroid-naïve patients with a positive methacholine test underwent capsaicin inhalation provocation on two occasions, before and after regular use of inhaled steroids over at least 3 months. Comparisons were made to 21 healthy controls. Sensitivity to methacholine and levels of exhaled nitric oxide were measured before and after the treatment. The participants also answered a validated questionnaire regarding environmental irritants. Results. The patients displayed higher capsaicin cough sensitivity than the controls before the treatment period, but not afterward. Before treatment, capsaicin cough answer correlated significantly with levels of exhaled nitric oxide, but not with methacholine sensitivity. After treatment with inhaled corticosteroids, the capsaicin cough sensitivity and the inflammatory parameters were normalized. In comparison to the control group, the patients reported more affective reactions to and behavioral disruptions induced by environmental irritants. Conclusions. In steroid-naïve patients with a positive methacholine test, there is a link between that part of the airway inflammation that is reflected by exhaled nitric oxide and that followed by an augmented reactivity of capsaicin-sensitive sensory nerves. This association disappears after steroid treatment.

Lung function, bronchial hyperresponsiveness, and atopy among firefighters

The aim of this study was to determine associations between lung function, bronchial hyperresponsiveness (BHR), and atopy with exposure to fire smoke among firefighters. The study was comprised of 402 firefighters, a randomly chosen subset of a previous survey among firefighters in the Netherlands. Subjects underwent spirometry and methacholine provocation, and blood samples were taken to assess atopy. Exposure to fire smoke was registered by a questionnaire. Hyperresponsiveness expressed as dose-response slope (DRS) was positively and significantly associated with the number of fires fought in the last 12 months with and without adjustments for smoking, gender, atopy, age, and exposure in the main job held. Limiting the analysis to firefighters without exposure within 7 days of testing did not change any of the associations. The association between the number of fires and the DRS was stronger among atopics, and hyperresponsiveness expressed as PD (20)was also significantly associated, indicating that atopics are at higher risk of developing BHR as a result of smoke exposure. Respiratory protection devices were not optimally used. It is recommended that awareness be heightened among firefighters to avoid exposure to all fire smoke and that management be sensitive to the adequate use of self-contained breathing apparatuses by their personnel.

Comparison of Bronchodilator Responsiveness After Methacholine-induced and AMP-induced Bronchoconstriciton in Asthmatic Children

RATIONALE: Airway Hyperresponsivness (AHR) and airway obstruction, relieved by bronchodilators are one of the main characteristics of asthma. We aimed to evaluate bronchodilator responsiveness (BDR) by applying a short-acting β-agonist (SABA) after methacholine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction, respectively.METHODS: Methacholine and AMP challenges were performed with 3 days of interval in 69 children with mild persistent to moderate asthma. They were followed up at the Allergy Clinic of Korea University Anam Hospital. Each provocation test was terminated when the FEV1 decreased by more than 20% of its baseline value. Fifteen minutes after SABA inhalation in the state of bronchoconstriction, BDR was evaluated by measuring the FEV1. Each subject was evaluated by serum total IgE, blood eosinophil counts and serum eosinophil cationic protein (ECP).RESULTS: BDR after methacholine challenge (30.7±18.0%) and AMP challenge (35.2±24.0%) showed no significant differences. BDR after AMP challenge showed a significant correlation with the serum total IgE, and blood eosinophil counts, and serum ECP, but not in the methacholine challenge.CONCLUSIONS: In asthmatic children, BDR after each methacholine and AMP provocation tests showed no differences. However, BDR after AMP challenge test showed a significant correlation with total IgE and blood eosinophilic inflammatory markers, compared to BDR after methacholine challenge test. RATIONALE: Airway Hyperresponsivness (AHR) and airway obstruction, relieved by bronchodilators are one of the main characteristics of asthma. We aimed to evaluate bronchodilator responsiveness (BDR) by applying a short-acting β-agonist (SABA) after methacholine- and adenosine 5'-monophosphate (AMP)-induced bronchoconstriction, respectively. METHODS: Methacholine and AMP challenges were performed with 3 days of interval in 69 children with mild persistent to moderate asthma. They were followed up at the Allergy Clinic of Korea University Anam Hospital. Each provocation test was terminated when the FEV1 decreased by more than 20% of its baseline value. Fifteen minutes after SABA inhalation in the state of bronchoconstriction, BDR was evaluated by measuring the FEV1. Each subject was evaluated by serum total IgE, blood eosinophil counts and serum eosinophil cationic protein (ECP). RESULTS: BDR after methacholine challenge (30.7±18.0%) and AMP challenge (35.2±24.0%) showed no significant differences. BDR after AMP challenge showed a significant correlation with the serum total IgE, and blood eosinophil counts, and serum ECP, but not in the methacholine challenge. CONCLUSIONS: In asthmatic children, BDR after each methacholine and AMP provocation tests showed no differences. However, BDR after AMP challenge test showed a significant correlation with total IgE and blood eosinophilic inflammatory markers, compared to BDR after methacholine challenge test.

Differences of the Clinical Manifestations and Laboratory Tests between Monosensitized and Polysensitized Children: A Single Center Study

Purpose: The objective of this study was to identify differences in the clinical manifestations and allergic indices between monosensitized and polysensitized children. Methods: We reviewed retrospective data from the medical records of patients who had chronic or recurrent respiratory symptoms and visited the pediatric clinic at Chung-Ang University Hospital for an evaluation of allergic diseases from January 2003 to January 2011. The patients were categorized into nonsensitized (n=111), monosensitized (n=149), and polysensitized (n=205) groups according to skin prick tests (as classified by five allergen groups). We compared gender, age, family history, admission history, food sensitization, total immunoglobulin E (IgE), peripheral eosinophil counts, eosinophil cationic protein (ECP) levels, forced expiratory volume in 1 second (FEV1), and methacholine provocation tests among the three groups. Results: The frequency of food sensitivity was highest in the polysensitized group (n=101, 49.3%), followed by the monosensitized (n=8, 5.4%) and nonsensitized groups (n=0) (P<0.001). The FEV1 was significantly lower in the polysensitized group than that in the monosensitized and nonsensitized groups (79.4 ± 20.2% vs. 87.2 ±16.0% vs. 87.6 ± 17.1%, respectively) (P=0.013). The total IgE and ECP levels were significantly higher in the polysensitized patients than those in the other patients (P<0.001 and <0.001, respectively). Differences in gender, age, peripheral eosinophil count, and bronchial hyper-responsiveness were not identified between the monosensitized and polysensitized groups. Conclusion: The polysensitized group showed more frequent food hypersensitivity, lower FEV1 values, and higher allergic indices such as total IgE and ECP, suggesting a different atopic phenotype compared with those in the monosensitized group. (Pediatr Allergy Respir Dis(Korea) 2011;21: 277-284)

Comparison of Exhaled Nitric Oxide Analyzers in Childhood Asthma

목 적: 호기산화질소(exhaled nitric oxide, eNO)는 천식환자의 기도염증을 반영하는 생물학적 지표로 잘 알려져 있지만, 검사 방법과 환자의 상태에 따라서 검사 결과가 달라질 수 있다. 본 연구에서는 소아 천식 환자에서 호기산화질소 측정기기 CLD88(R) (Ecomedics; Durnten, Switzerland) 과 Niox mino(R) (Aerocrine; Solna, Sweden) 의 호기산화질소 측정치를 비교하고 그 임상적 의의를 알아보고자 하였다. 방법: 세브란스 어린이병원에 내원한 천식환자 104명, 대조군 59명을 대상으로 하였으며 Niox mino(R)와 CLD88(R)을 이용하여 호기산화질소를 측정하고, 기관지확장제 투여 전후 폐기능검사, 메타콜린 유발시험, 유도객담검사를 시행하였다. 결과: Niox mino(R)로 측정한 호기산화질소는 천식군(38.4±27.9 ppb)에서 대조군(17.2±9.0 ppb, P<0.001)에 비해 유의하게 높았고, CLD88(R)을 이용한 경우에도 천식군(47.8±31.8 ppb)에서 대조군(22.2±12.7 ppb, P<0.001)보다 높았다. 측정치는 Niox mino(R)로 측정한 경우약 9.0 ppb 낮았다. 측정치의 급내상관계수(intraclass correlation coefficient)는 0.786(P<0.001)이었다. 호기산화질소 농도는 폐기능의 지표 중 FEV1/FVC, 유도 객담 내 호산구 비율과 유의한 상관관계를 보였으며, PC20 농도와는 전체를 대상으로 분석하는 경우 유의한 상관관계를 보였으나, 천식환자만을 대상으로 분석하였을 때에는 유의한 상관관계를 보이지 않았다. 결론: 호기산화질소 측정치는 Niox mino(R)와 CLD88(R)로 측정한 모두에서 천식군에서 대조군에 비하여 유의하게 높으므로 천식의 보조적인 진단도구로 사용될 수 있을 것으로 생각된다. 그러나 측정 기기에 따라 호기산화질소 농도의 측정치가 다를 수 있음을 유의해야 한다.

Electronic nose breathprints are independent of acute changes in airway caliber in asthma.

Molecular profiling of exhaled volatile organic compounds (VOC) by electronic nose technology provides breathprints that discriminate between patients with different inflammatory airway diseases, such as asthma and COPD. However, it is unknown whether this is determined by differences in airway caliber. We hypothesized that breathprints obtained by electronic nose are independent of acute changes in airway caliber in asthma. Ten patients with stable asthma underwent methacholine provocation (Visit 1) and sham challenge with isotonic saline (Visit 2). At Visit 1, exhaled air was repetitively collected pre-challenge, after reaching the provocative concentration (PC20) causing 20% fall in forced expiratory volume in 1 second (FEV1) and after subsequent salbutamol inhalation. At Visit 2, breath was collected pre-challenge, post-saline and post-salbutamol. At each occasion, an expiratory vital capacity was collected after 5 min of tidal breathing through an inspiratory VOC-filter in a Tedlar bag and sampled by electronic nose (Cyranose 320). Breathprints were analyzed with principal component analysis and individual factors were compared with mixed model analysis followed by pairwise comparisons. Inhalation of methacholine led to a 30.8 ± 3.3% fall in FEV1 and was followed by a significant change in breathprint (p = 0.04). Saline inhalation did not induce a significant change in FEV1, but altered the breathprint (p = 0.01). However, the breathprint obtained after the methacholine provocation was not significantly different from that after saline challenge (p = 0.27). The molecular profile of exhaled air in patients with asthma is altered by nebulized aerosols, but is not affected by acute changes in airway caliber. Our data demonstrate that breathprints by electronic nose are not confounded by the level of airway obstruction.

Problematic severe asthma: A proposed approach to identifying children who are severely resistant to therapy

Children with problematic severe asthma (PA) are either difficult to treat because of the presence of aggravating factors or else severely resistant to therapy. We investigated a cohort of school-aged children with PA and compared these children to age-matched peers with controlled persistent asthma (CA). The aims were to characterize features of children suffering from PA and identify children who were severely resistant to therapy. In this cross-sectional, multicenter comparison of children with different manifestations of persistent asthma, PA was defined as insufficient asthma control despite level 4 treatment, according to GINA. The protocol included questionnaires, spirometry, methacholine provocation, measurement of fraction of nitric oxide in exhaled (FE(NO) ) and nasal air, blood sampling for inflammatory biomarkers and atopy, and computerized tomography of sinuses and lungs (in the PA group only). Of the 54 children with PA, 61% had therapy-resistant asthma, with the remaining being difficult to treat because of identified aggravating factors. Children with PA more often had parents with asthma (p=0.003), came from families with a lower socioeconomic status (p=0.01), were less physically active (p=0.04), and had more comorbidity with rhinoconjunctivitis (p=0.01) than did the 39 children with CA. The former also exhibited lower FEV(1) values (p=0.02) and increased bronchial hyper-responsiveness (p=0.01), but there were no differences in atopy (p=0.81) or FE(NO) (p=0.16). A non-invasive protocol, involving a standardized and detailed clinical characterization, revealed distinguishing features of children with PA and enabled the identification of children with therapy-resistant asthma.

The Best Next Step After Inhaled Steroids to Control Asthma

Research Article| July 01 2010 The Best Next Step After Inhaled Steroids to Control Asthma AAP Grand Rounds (2010) 24 (1): 2. https://doi.org/10.1542/gr.24-1-2 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation The Best Next Step After Inhaled Steroids to Control Asthma. AAP Grand Rounds July 2010; 24 (1): 2. https://doi.org/10.1542/gr.24-1-2 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: asthma, inhaled corticosteroid Source: Lemanske RF, Mauger DT, Sorkness CA, et al. Step-up therapy for children with uncontrolled asthma while receiving inhaled corticosteroids. N Engl J Med. 2010; 362(11): 975– 985; doi: https://doi.org/10.1056/NEJMoa1001278Google Scholar To determine the best add-on therapy for children with uncontrolled asthma despite the use of conventional low-dose fluticasone (100 μg twice daily), the Childhood Asthma Research and Education Network conducted a randomized triple crossover trial in children 6 to 17 years of age from five US institutions. From 2007 through 2008, children with a physician diagnosis of mild-to-moderate asthma, an ability to perform spirometry, and either a 12% increase in FEV1 response to bronchodilator or a methacholine provocation of 12.5 mg/ml or less causing a 20% fall in FEV1 were enrolled. Participants completed three treatment interventions in random order. Each treatment study period lasted 16 weeks with a four-week washout period between the second and third study periods. The treatments were: fluticasone 250 μg twice daily (inhaled-corticosteroid [ICS] step-up therapy); 100 μg fluticasone plus a long-acting bronchodilator (LABA), salmeterol, 50 μg twice daily (as Advair); or 100 μg fluticasone plus 5 or 10 mg of the leukotriene-receptor antagonist (LTRA) montelukast (Singulair). The primary outcome was the differential response to each of the three step-up therapies for the following asthma control measures: the need for treatment with oral prednisone for acute asthma exacerbations, the number of asthma control days, and FEV1. Of the 182 enrolled participants, 165 completed at least two of the 16-week crossover periods, and 157 completed all three. Nearly all the children had a differential response to each step-up therapy. In pairwise comparisons, a significantly greater proportion of subjects had a better response to LABA than to either LTRA (relative probability, 1.6; 95% CI, 1.1–2.3; P=.004) or ICS (relative probability, 1.7; 95% CI, 1.2–2.4; P=.002). Better control at baseline predicted a better response to LABA step-up (P=.009). The authors conclude that there is a ceiling effect of low-dose inhaled corticosteroids in many, though not all, children and that improvement in asthma control requires the addition of a different class of medication. Furthermore, the addition of a LABA was significantly more likely to provide a better response than an increased dose of inhaled corticosteroid or addition of a LTRA. This report’s conclusion is consistent with previous studies in adults demonstrating that the addition of a LABA is more likely to provide greater clinical benefit than an increased dosage of an inhaled corticosteroid,1 and that the additive effect of a LTRA is modest.2 The FDA warning about the LABAs3 applies primarily to use as single agents without an inhaled corticosteroid. However, data recently reviewed in these pages identified an increased risk of asthma exacerbations among the minority of children with a polymorphism of the β2 adrenergic receptor receiving either a LABA or daily albuterol (see AAP Grand Rounds, May 2010;23:554). Exceptional... You do not currently have access to this content.

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats

Although chronic normobaric hypoxia (CH) alters lung function, its potential to induce bronchial hyperreactivity (BHR) is still controversial. Thus the effects of CH on airway and tissue mechanics separately and changes in lung responsiveness to methacholine (MCh) were investigated. To clarify the mechanisms, mechanical changes were related to end-expiratory lung volume (EELV), in vivo results were compared with those in vitro, and lung histology was assessed. EELV was measured plethysmographically in two groups of rats exposed to 21 days of CH (11% O(2)) or to normoxia. Total respiratory impedance was measured under baseline conditions and following intravenous MCh challenges (2-18 microg x kg(-1) x min(-1)). The lungs were then excised and perfused, and the pulmonary input impedance was measured, while MCh provocations were repeated under a pulmonary capillary pressure of 5, 10, and 15 mmHg. Airway resistance, tissue damping, and elastance were extracted from the respiratory impedance and pulmonary input impedance spectra. The increases in EELV following CH were associated with decreases in airway resistance, whereas tissue damping and elastance remained unaffected. CH led to the development of severe BHR to MCh (206 +/- 30 vs. 95 +/- 24%, P < 0.001), which was not detectable when the same lungs were studied in vitro at any pulmonary capillary pressure levels maintained. Histology revealed pulmonary arterial vascular remodeling with overexpression of alpha-smooth muscle actin antibody in the bronchial wall. These findings suggest that, despite the counterbalancing effect of the increased EELV, BHR develops following CH, only in the presence of intact autonomous nervous system. Thus neural control plays a major role in the changes in the basal lung mechanics and responsiveness following CH.

Infection Rate ofChlamydia pneumoniaein Patients with Chronic Cough

Background: Persistent cough has recently been found to be associated with Chlamydia pneumoniae infection. We aimed to investigate the infection rate of C. pneumonia in adult patients with chronic cough. Methods: We recruited 68 patients with persistent cough lasting in excess of 3 weeks, who visited Kangdong Sacred Heart Hospital from January 2005 to August 2005. On the first visit, chest and paranasal sinuses radiography, skin prick test of common allergens, and induced sputum samples for C. pneumoniae were performed in all of patients. Further evaluation for diagnosis included a methacholine provocation test and eosinophil counts in induced sputum. Results: The most common cause of chronic cough was upper airway cough syndrome (UACS) (26.5%), followed by eosinophilic bronchitis (20.6%) and cough variant asthma (16.2%). Idiopathic chronic cough was the cause in 33.8% of patients. The mean duration of cough was 11.7 months. C. pneumoniae was isolated by polymerase chain reaction (PCR) from one patient who had upper respiratory air way syndrome. Conclusion: Chlamydia pneumoniae appears to have a minor role as a cause of chronic cough in patients.

Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting β 2-agonist, in patients with mild asthma

Long-acting ss(2)-agonists are an established controller medication in asthma. BI 1744 is a novel L\long-acting ss(2)-agonist with a preclinical profile that suggests 24-hour bronchodilation and bronchoprotection may be achieved. To examine the bronchoprotective effects of single doses of BI 1744 against methacholine provocation in subjects with mild asthma. Thirty-one subjects with mild asthma were randomized to receive single doses of BI 1744 (2, 5, 10, 20 microg) or placebo on separate days according to a double-blind, 5-way crossover design. Methacholine challenges were performed at 30 minutes and at 4, 8, 24, and 32 hours after each single dose of medication, and the results were expressed as PC(20) FEV(1). All doses of BI 1744 produced statistically significant increases in the methacholine PC(20) compared with placebo as long as 32 hours. The mean (geometric SEM) methacholine PC(20) 24 hours after dosing with placebo was 1.73 (1.13) mg/mL, which increased after 2 microg to 3.86 (1.14) mg/mL, after 5 microg to 5.67 (1.14) mg/mL, after 10 microg to 9.42 (1.13) mg/mL, and after 20 microg to 13.71 (1.14) mg/mL (all P < .0001). After 32 hours, the methacholine PC(20) value remained significantly increased for all doses. No safety or tolerability concerns were identified. BI 1744 provides significant bronchoprotection against inhaled methacholine for up to 32 hours after single-dose administration.

Impact of elevated pulmonary blood flow and capillary pressure on lung responsiveness

Since alterations in pulmonary hemodynamics may lead to airway hyperreactivity, the consequences of individual changes in pulmonary blood flow (Qp) and capillary pressure (Pc) on lung responsiveness were investigated. During maintenance of a steady-state Pc of 5, 10, or 15 mmHg (groups 1-3), acute increases of Qp were generated in isolated, perfused rat lungs by simultaneous pulmonary arterial pressure elevation and venous pressure lowering. Conversely, at constant low (groups 4 and 5) or high Qp (groups 6 and 7), Pc was lowered or elevated by changing, in parallel, the pulmonary arterial and venous pressures. Pulmonary input impedance was measured under baseline conditions and during methacholine provocation (2-18 microg*kg(-1)*min(-1)), whereas the pulmonary hemodynamics were altered in accordance with the group allocation. The airway resistance and constant-phase parenchymal model parameters were identified from the pulmonary input impedance spectra. Increases of Qp at constant Pc had no effect on the basal lung mechanics, whereas they enhanced the lung reactivity to methacholine, particularly when high Pc was maintained [peak airway resistance increases of 299 +/- 99% (SE) vs. 609 +/- 217% at Qp levels of 5 and 10 ml/min, respectively, P < 0.05]. In contrast, the change of Pc at constant Qp slightly deteriorated the basal parenchymal mechanics without affecting the lung responsiveness. These findings suggest that increases in Qp per se may lead to the development of airway hyperreactivity. This phenomenon may contribute to the airway susceptibility under conditions associated with simultaneous elevations in pulmonary vascular pressures and Qp, such as exercise-induced asthma and the situation in children with congenital heart diseases.